Clinical Association Of Siclec15 In Gastric Adenocarcinomas Patients

The identification of novel biomarkers for diagnosis and prognosis of Gastric Cancer (GC) is pivotal to reduce disease-associated mortality. Previous studies have reported that Siglec-15 is overexpressed on human cancer, including colon, thyroid, lung, liver. The Siglecs are a group of sialic-acid-binding immunoglobulin-like lectins, involved in cell-cell and cell-pathogen interactions. Recently, it was reported that Siglec-15 could be a potential target for cancer immunotherapy, because it supresses T cell activity and its expression with PD-L1 are mutually exclusive. However, the relationship between the expression of Siglec-15 in GC pathological and outcome parameters were not investigated. Therefore, the purpose of this study was to evaluate the expression of SIGLEG15 in gastric adenocarcinomas patients and correlated the expression patterns with each other and with some clinicopathological variables. Surgical specimens of GC tissue and adjacent normal mucosa obtained from 67 patients were examined. The patients underwent gastrectomy at the Hospital do Cancer de Pernambuco, Brazil, between 2013 and 2016. Informed consent was obtained from each patient, with all protocols approved by the ethics committee9s (CAAE: 39976214.90000.5205). Protein expression was examined by immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded (FFPE) specimens. The primary anti-SIGLEC15 antibody were used and positive control was performed on a tissue model indicated on the data sheet and reference sources (The Human Protein Atlas). Samples that demonstrated enzyme staining in more than 10% of the neoplastic cells in different degrees of intensity were considered positive and those that did not present were negative. Of 67 GC patients, 52 (77.61%) were SIGLEC-15 positive and 15 patients (25.38%) were negative. In 40 samples (59.70%) of the 67 patients analysed presented an adjacent normal tissue, in which 14 (35%) were SIGLEC-15 positive, specially in productions cells of the gastric glands and in the ducts. In neoplastic lesions, SIGLEC-15 was observed in the cytoplasm in 13 samples (19.40%), perinuclear in 4 (5.97%) and nuclear in 1 only sample (1.49%). On the other hand, combinations of cytoplasmic, nuclear and perinuclear staining were observed in 44 samples (61.9%). Expression of SIGLEC-15 was significantly associated with age (p=0.047), with tumor differentiation (p=0.002), angiolymphatic invasion (p=0.02) and surgical staging (p=0.056). Additional analysis, including sex, type of surgery, initial treatment, nodal status, radiotherapy, chemotherapy, lymph node, H.Pylory infection and overall and disease-free survival were not significant. High Siglec-15 expression in gastric cancer could be a novel biomarker for surgical staging and vascular invasion. Further studies with a larger group of patients and experimental assays are required to elucidate Siglec-15 role in gastric cancer. Citation Format: Michelly Cristiny Pereira, Michael Williames Quirino, Antonio Felix Silva Filho, Mario Rino Martins, Maira Galdino da Rocha Pitta, Moacyr Jesus Barreto de Melo Rego. Clinical Association of Siclec15 in gastric adenocarcinomas patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6481.